Medical Pharmacology Chapter 36: Antiviral Drugs
Anti-viral drugs with activity against influenza.
Drug Absorption and Elimination
Following oral administration, both amantadine and rimantadine are well absorbed.1
Elderly patients require about one-half of the weight-adjusted amantadine dose required for young adults in order to obtain trough plasma levels of 0.3 µg/ml.
Both drugs exhibit very large volumes of distribution (Vd).
Amantadine is found in breast milk.
Amantadine is excreted by the kidney, mainly in an unmetabolized form following glomerular filtration and tubular secretion.1
The plasma half-life elimination is about 12-18 hours in young adults.
Given the dependence on renal function for drug elimination, in elderly patients and to a greater extent in those with renal impairment, elimination half-life may increase up to two fold.
Dose adjustments are appropriate in patients with mild renal impairment.1
By contrast, rimantadine is metabolized mainly by hydroxylation, conjugation and glucuronidation before renal excretion occurs.
After oral dosing, the elimination half-life of rimantadine ranges from 24-36 hours with 60%-90% excreted in the urine as metabolites.1
Common adverse effects are both gastrointestinal and central nervous system-related.3
Gastrointestinal effects include:
CNS side effects include:
Side effects are dose-related and may decrease following continual drug treatment, even disappearing after one week of administration.3
The more serious CNS side effects including delirium, hallucinations, agitation and others may be related to amantadine effects on dopamine neurotransmission.
These effects appear less likely with rimantadine administration compared to amantadine.
CNS adverse effects may be more likely in patients with renal insufficiency, given amantadine clearance is mediated by the kidney, pre-existing seizure disorders or in elderly patients.
Administration of amantadine with other drugs including anticholinergic agents, hydrochlorothiazide (a diuretic), antihistamines, and trimethoprim-sulfamethoxazole may result in an increased incidence of adverse reactions.
Both amantadine and rimantadine are found teratogenic and embryotoxic in the rat model.3
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